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Best, PhD Department of Biostatistics *Consolidated Standards of Reporting Trials(-,-,AcknowledgementsThis presentation is about the work of others. See: Moher D, Schulz KF, Altman DG for The CONSORT Group.  The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials. JAMA. 2001. 285:1987-91. DG Altman, KF Schulz, D Moher, M Egger, F Davidoff, D Elbourne, Peter C. Gtzsche, and T Lang, MA, for the CONSORT Group.  The Revised CONSORT Statement for Reporting Randomized Trials: Explanation and Elaboration. Annals of Internal Medicine, 2001. 134(8), 663-694.X44P4 Q&\Remember?: Stampfer MJ, et al. Post-menopausal estrogen therapy and cardiovascular disease: ten-year follow-up from the Nurses Health Study. N Engl J Med. 1991;325:756-762. 8  , }abstract: The effect of postmenopausal estrogen therapy on the risk of cardiovascular disease remains controversial. & METHODS. We followed 48,470 postmenopausal women, 30 to 63 years old, who were participants in the Nurses' Health Study, ... During up to 10 years of follow-up & . RESULTS. After adjustment for age and other risk factors, the overall relative risk of major coronary disease in women currently taking estrogen was 0.56 (95 percent confidence interval, 0.40 to 0.80); & CONCLUSIONS. Current estrogen use is associated with a reduction in the incidence of coronary heart disease as well as in mortality from cardiovascular disease, & .Z^8R' Later, Contradicted FindingsThe Women s Health Initiative, a large randomized trial, found that estrogen and progestin significantly increased the relative risk of coronary events by 29% among postmenopausal women. Refuting results were also seen in another large randomized trial, the Heart and Estrogen/progestin Replacement Study (HERS). Many reviews have documented deficiencies in reports of clinical trials. Ni $! From the JAMA abstract$  To comprehend the results of a randomized controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Consolidated Standards of Reporting Trials) statement to help authors improve reporting by using a checklist and flow diagram.:C$JAMA abstract continued $$BThe revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. & The revised flow diagram depicts information from 4 stages of a trial (enrollment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, according to each intervention group, included in the primary data analysis.|"9 U S JAMA abstract continued $$RIn sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial s conduct and to assess the validity of its results\`        Annals Abstract begins $$Overwhelming evidence now indicates that the quality of reporting of randomized, controlled trials (RCTs) is less than optimal. Recent methodologic analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which boast the elimination of systematic error as their primary hallmark. Systematic error in RCTs reflects poor science, and poor science threatens proper ethical standards.-  )a&eOther Study Designs<Endorsement: The International Committee of Medical Journal Editors, BMJ, Lancet, JAMA, Annals of Int. Med., and others But: Not every trial is a parallel-group, randomized, double-blind, placebo-controlled clinical trial. Still standards trickle down to proposed standards in: Meta-analyses, observational studies.$=F' FTitle and Abstract #1 How participants were allocated to interventions2G" 1" * Random assignment is the preferred method [to assign treatment or other interventions to trial participants]; & three major advantages. First it eliminates bias in the assignment of treatments. Without randomization, treatment comparisons may be prejudiced, whether consciously or not, by selection of participants of a particular kind to receive a particular treatment. Second, random allocation facilitates blinding the identity of treatments to the investigators, participants, and evaluators, possibly by use of a placebo, which reduces bias after assignment of treatments. Third, random assignment permits the use of probability theory to express the likelihood that any difference in outcome between intervention groups merely reflects chance. Preventing selection and confounding biases is the most important advantage of randomization.N* %. T* . * . * . (* .  *  . 3*  BIntroduction #2 Scientific background and explanation of rationale C 4 The Helsinki Declaration states that biomedical research involving people should be based on a thorough knowledge of the scientific literature. That is, it is unethical to expose human subjects unnecessarily to the risks of research.  1Methods #3 Eligibility criteria for participants 2  ( & usually restrict this population by using eligibility criteria and by performing the trial in one or a few centers. Careful descriptions of the trial participants and the setting in which they were studied are needed so that readers may assess the external validity (generalizability) of the trial results (see item 21). Of particular importance is the method of recruitment, such as by referral or self-selection (for example, through advertisements). :/EP <#3b The settings and locations where the data were collected =$:$& institutions vary greatly in their organization, experience, and resources and the baseline risk for the medical condition under investigation. Climate and other physical factors, economics, geography, and the social and cultural milieu can all affect a study s external validity. #14 Dates defining the periods of recruitment and follow-up Knowing when a study took place and over what period participants were recruited places the study in historical context. Xz"9e p#4 Precise details of the interventions intended for each group and how and when they were actually administeredPq&+What is meant by  control group ? In what sense  placebo ? What is  usual care ?%#5 Specific objectives and hypotheses &($(Objectives are the questions that the trial was designed to answer. Hypotheses are prespecified questions being tested. Majority provide adequate info about these. Vz,16,#6 Clearly defined primary and secondary outcome measures& any methods used to enhance the quality of measurements  sqThe primary & is the prespecified outcome of greatest importance and is usually the one used in the sample size calculation. & Having more than one or two outcomes& is not recommended. All outcome measures & completely defined. & indicate the prespecified time point & specify who assessed outcomes & and how many assessors. & instruments. & previously developed and validated scales. full details of how & . measured & steps taken to increase the reliability of the measurements.  e X? $[#7 How sample size was determined and, explanation of interim analyses and stopping rules  \YFor scientific and ethical reasons, the sample size for a trial needs to be planned carefully, with a balance between clinical and statistical considerations. Ideally, a study should be large enough to have a high probability (power) of detecting as statistically significant a clinically important difference of a given size if such a difference exists. Authors should report whether they took multiple  looks at the data and, if so, how many there were, the statistical methods used & :d:5BU(4Assessing the likelihood of bias in group assignment55#8a Method used to generate the allocation sequence Blocking, Stratification, Minimization of Imbalance #9 Method used to implement the random allocation sequence), clarifying whether the sequence was concealed until interventions were assigned Without adequate allocation concealment, even random, sequences can be subverted. #10 Who generated the allocation sequence, who enrolled participants, and who assigned participants to their groups. 44Rv4 rR v-#11a Whether or not participants, those administering the interventions, and those assessing the outcomes were blinded to group assignment.k"Patient blinding: may influence treatment effect & placebo effect & compliance bias Staff blinding: performance bias & withdrawal bias Outcome blinding: observer bias Analyst blinding: influence choice of strategies #11b If done, how the success of blinding was evaluated 8 3 (.#12a Statistical methods used to compare groups for primary outcome(s) & additional analyses, such as subgroup analyses and adjusted analyses  It is essential to specify which statistical procedure was used for each analysis. & more than one observation per patient. Because of the high risk for spurious findings, subgroup analyses are often discouraged. Post hoc subgroup comparisons are especially likely not to be confirmed by further studies. Such analyses do not have great credibility. & imbalances in characteristics are adjusted for by using some form of multiple regression analysis. & adjusted analyses should be specified in the study protocol. S)S)YT-g<4Q#13 Flow of participants through each stage (a diagram is strongly recommended). 2R$)$$#Specifically, for each group report the numbers of participants randomly assigned, receiving intended treatment, completing the study protocol, and analyzed for the primary outcome. a trial of chiropractic manipulation of the cervical spine for treatment of episodic tension-type headache. $$k<C#15 Baseline demographic and clinical characteristics of each group D A & it is important to know the characteristics of the participants who were actually recruited. This information allows readers, especially clinicians, to judge how relevant the results of a trial might be to a particular patient. :KC/=v#16 Number of participants (denominator) in each group included in each analysis and whether the analysis was by  intention to treat. State the results in absolute numbers when feasible  e.g., 10 of 20, not 50%. & results should not be presented solely as summary measures, such as relative risks. Intention-to-treat analysis is generally favored because it avoids bias associated with nonrandom loss of participants. & make clear which participants are included in each analysis. Intention-to-treat analysis is not appropriate for examining adverse effects. X&O:O?#17 For each primary and secondary outcome, a summary of results for each group and the estimated effect size and its precision 8aEffect Size: the contrast between the groups. For binary outcomes, & the risk ratio (relative risk), odds ratio, or risk difference; for survival time data, & the hazard ratio or difference in median survival time; for continuous data, & the difference in means. Confidence intervals should be presented for the contrast between groups. A common error is the presentation of separate confidence intervals for the outcome in each group rather than for the treatment effect./<E 6  D #18 Address multiplicity by reporting any other analyses performed, including subgroup analyses and adjusted analyses, indicating those prespecified and those exploratory Multiple analyses of the same data create a considerable risk for false-positive findings. Authors should especially resist the temptation to perform many subgroup analyses. Analyses that were prespecified in the trial protocol are much more reliable than those suggested by the data. : ,.E!K#19 All important adverse events or side effects in each intervention group LIMost interventions have unintended and often undesirable effects in addition to intended effects. Many reports of RCTs provide inadequate information on adverse events. In 192 reports of drug trials, only 39% had adequate reporting of clinical adverse events and 29% had adequate reporting of laboratory-determined toxicity. Furthermore, in one volume of a prominent general medical journal in 1998, 58% (30 of 52) of reports (mostly RCTs) did not provide any details on harmful consequences of the interventions.<b("F" Discussion#20 Interpretation of the results, taking into account study hypotheses, sources of potential bias or imprecision, and the dangers associated with multiplicity of analyses and outcomes. x74  9G#Annals recommendationsXStructure the discussion section by presenting 1) a brief synopsis of the key findings; 2) consideration of possible mechanisms and explanations; 3) comparison with relevant findings from other published studies & ; 4) limitations of the present study (and methods used to minimize and compensate for those limitations); 5) a brief section that summarizes the clinical and research implications of the work, as appropriate. 0}0 / -  H$>#21 Generalizability (external validity) of the trial findings ?$<$Shadish, Cook and Campbell:  Most experiments are highly local but have general aspirations . That is, there can be a conflict between the localized nature of the information in a paper and the desire of the authors to claim that their findings generalize to other people, in other settings, with comparable interventions, and other outcomes. & Cronbach: a question of external validity. That is, do  instances on which data are collected & generalize to the units, treatments, variables and settings not directly observed ?Z_>$TI%L#22 General interpretation of the results in the context of current evidence M J The result of an RCT is important regardless of which treatment appears better, magnitude of effect, or precision. Readers will want to know how the present trial s results relate to those of other published RCTs. This discussion should be as systematic as possible and not limited to studies that support the results of the current trial.W)SummaryA critical review of most journal articles would yield suggestions for improvement. 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Best, PhD Department of Biostatistics *Consolidated Standards of Reporting Trials(-,-,AcknowledgementsThis presentation is about the work of others. See: Moher D, Schulz KF, Altman DG for The CONSORT Group.  The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials. JAMA. 2001. 285:1987-91. DG Altman, KF Schulz, D Moher, M Egger, F Davidoff, D Elbourne, Peter C. Gtzsche, and T Lang, MA, for the CONSORT Group.  The Revised CONSORT Statement for Reporting Randomized Trials: Explanation and Elaboration. Annals of Internal Medicine, 2001. 134(8), 663-694.X44P4 Q&\Remember?: Stampfer MJ, et al. Post-menopausal estrogen therapy and cardiovascular disease: ten-year follow-up from the Nurses Health Study. N Engl J Med. 1991;325:756-762. 8  , }abstract: The effect of postmenopausal estrogen therapy on the risk of cardiovascular disease remains controversial. & METHODS. We followed 48,470 postmenopausal women, 30 to 63 years old, who were participants in the Nurses' Health Study, ... During up to 10 years of follow-up & . RESULTS. After adjustment for age and other risk factors, the overall relative risk of major coronary disease in women currently taking estrogen was 0.56 (95 percent confidence interval, 0.40 to 0.80); & CONCLUSIONS. Current estrogen use is associated with a reduction in the incidence of coronary heart disease as well as in mortality from cardiovascular disease, & .Z^8R' Later, Contradicted FindingsThe Women s Health Initiative, a large randomized trial, found that estrogen and progestin significantly increased the relative risk of coronary events by 29% among postmenopausal women. Refuting results were also seen in another large randomized trial, the Heart and Estrogen/progestin Replacement Study (HERS). Many reviews have documented deficiencies in reports of clinical trials. Ni $! From the JAMA abstract$  To comprehend the results of a randomized controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Consolidated Standards of Reporting Trials) statement to help authors improve reporting by using a checklist and flow diagram.:C$JAMA abstract continued $$BThe revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. & The revised flow diagram depicts information from 4 stages of a trial (enrollment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, according to each intervention group, included in the primary data analysis.|"9 U S JAMA abstract continued $$RIn sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial s conduct and to assess the validity of its results\`        Annals Abstract begins $$Overwhelming evidence now indicates that the quality of reporting of randomized, controlled trials (RCTs) is less than optimal. Recent methodologic analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which boast the elimination of systematic error as their primary hallmark. Systematic error in RCTs reflects poor science, and poor science threatens proper ethical standards.-  )a&eOther Study Designs<Endorsement: The International Committee of Medical Journal Editors, BMJ, Lancet, JAMA, Annals of Int. Med., and others But: Not every trial is a parallel-group, randomized, double-blind, placebo-controlled clinical trial. Still standards trickle down to proposed standards in: Meta-analyses, observational studies.$=F' FTitle and Abstract #1 How participants were allocated to interventions2G" 1" * Random assignment is the preferred method [to assign treatment or other interventions to trial participants]; & three major advantages. First it eliminates bias in the assignment of treatments. Without randomization, treatment comparisons may be prejudiced, whether consciously or not, by selection of participants of a particular kind to receive a particular treatment. Second, random allocation facilitates blinding the identity of treatments to the investigators, participants, and evaluators, possibly by use of a placebo, which reduces bias after assignment of treatments. Third, random assignment permits the use of probability theory to express the likelihood that any difference in outcome between intervention groups merely reflects chance. Preventing selection and confounding biases is the most important advantage of randomization.N* %. T* . * . * . (* .  *  . 3*  BIntroduction #2 Scientific background and explanation of rationale C 4 The Helsinki Declaration states that biomedical research involving people should be based on a thorough knowledge of the scientific literature. That is, it is unethical to expose human subjects unnecessarily to the risks of research.  1Methods #3 Eligibility criteria for participants 2  ( & usually restrict this population by using eligibility criteria and by performing the trial in one or a few centers. Careful descriptions of the trial participants and the setting in which they were studied are needed so that readers may assess the external validity (generalizability) of the trial results (see item 21). Of particular importance is the method of recruitment, such as by referral or self-selection (for example, through advertisements). :/EP <#3b The settings and locations where the data were collected =$:$& institutions vary greatly in their organization, experience, and resources and the baseline risk for the medical condition under investigation. Climate and other physical factors, economics, geography, and the social and cultural milieu can all affect a study s external validity. #14 Dates defining the periods of recruitment and follow-up Knowing when a study took place and over what period participants were recruited places the study in historical context. Xz"9e p#4 Precise details of the interventions intended for each group and how and when they were actually administeredPq&+What is meant by  control group ? How is the  placebo made to be indistinguishable from the test intervention? What is  usual care ?%#5 Specific objectives and hypotheses &($(Objectives are the questions that the trial was designed to answer. Hypotheses are prespecified questions being tested. The majority of papers provide adequate info about these. Vz:16:#6 Clearly defined primary and secondary outcome measures& methods used to enhance the quality of measurements  omThe primary       !"#$'()*+& is the prespecified outcome of greatest importance and is usually the one used in the sample size calculation. & Having more than one or two outcomes& is not recommended. All outcome measures & completely defined. & indicate the prespecified time point & specify who assessed outcomes & and how many assessors. & instruments. & previously developed and validated scales. full details of how & . measured & steps taken to increase the reliability of the measurements.  e X? $[#7 How sample size was determined and, explanation of interim analyses and stopping rules  \YFor scientific and ethical reasons, the sample size for a trial needs to be planned carefully, with a balance between clinical and statistical considerations. Ideally, a study should be large enough to have a high probability (power) of detecting as statistically significant a clinically important difference of a given size if such a difference exists. Authors should report whether they took multiple  looks at the data and, if so, how many there were, the statistical methods used & :d:5BU(4Assessing the likelihood of bias in group assignment55#8 Method used to generate the allocation sequence Blocking, Stratification, Minimization of Imbalance #9 Method used to implement the random allocation sequence), clarifying whether the sequence was concealed until interventions were assigned Without adequate allocation concealment, even random, sequences can be subverted. #10 Who generated the allocation sequence, who enrolled participants, and who assigned participants to their groups. 34Rv4 rR v-#11a Whether or not participants, those administering the interventions, and those assessing the outcomes were blinded to group assignment.k"Patient blinding: may influence treatment effect & placebo effect & compliance bias Staff blinding: performance bias & withdrawal bias Outcome blinding: observer bias Analyst blinding: influence choice of strategies #11b If done, how the success of blinding was evaluated 8 3 (.#12a Statistical methods used to compare groups for primary outcome(s) & additional analyses, such as subgroup analyses and adjusted analyses  It is essential to specify which statistical procedure was used for each analysis. & more than one observation per patient. Because of the high risk for spurious findings, subgroup analyses are often discouraged. Post hoc subgroup comparisons are especially likely not to be confirmed by further studies. Such analyses do not have great credibility. & imbalances in characteristics are adjusted for by using some form of multiple regression analysis. & adjusted analyses should be specified in the study protocol. S)S)YT-g<4Q#13 Flow of participants through each stage (a diagram is strongly recommended). 2R$)$$#Specifically, for each group report the numbers of participants randomly assigned, receiving intended treatment, completing the study protocol, and analyzed for the primary outcome. a trial of chiropractic manipulation of the cervical spine for treatment of episodic tension-type headache. $$k<C#15 Baseline demographic and clinical characteristics of each group D A & it is important to know the characteristics of the participants who were actually recruited. This information allows readers, especially clinicians, to judge how relevant the results of a trial might be to a particular patient. :KC/=v#16 Number of participants (denominator) in each group included in each analysis and whether the analysis was by  intention to treat. State the results in absolute numbers when feasible  e.g., 10 of 20, not 50%. & results should not be presented solely as summary measures, such as relative risks. Intention-to-treat analysis is generally favored because it avoids bias associated with nonrandom loss of participants. & make clear which participants are included in each analysis. Intention-to-treat analysis is not appropriate for examining adverse effects. X&O:O?#17 For each primary and secondary outcome, a summary of results for each group and the estimated effect size and its precision 8aEffect Size: the contrast between the groups. For binary outcomes, & the risk ratio (relative risk), odds ratio, or risk difference; for survival time data, & the hazard ratio or difference in median survival time; for continuous data, & the difference in means. Confidence intervals should be presented for the contrast between groups. A common error is the presentation of separate confidence intervals for the outcome in each group rather than for the treatment effect./<E 6  D #18 Address multiplicity by reporting any other analyses performed, including subgroup analyses and adjusted analyses, indicating those prespecified and those exploratory Multiple analyses of the same data create a considerable risk for false-positive findings. Authors should especially resist the temptation to perform many subgroup analyses. Analyses that were prespecified in the trial protocol are much more reliable than those suggested by the data. : ,.E!K#19 All important adverse events or side effects in each intervention group LIMost interventions have unintended and often undesirable effects in addition to intended effects. Many reports of RCTs provide inadequate information on adverse events. In 192 reports of drug trials, only 39% had adequate reporting of clinical adverse events and 29% had adequate reporting of laboratory-determined toxicity. Furthermore, in one volume of a prominent general medical journal in 1998, 58% (30 of 52) of reports (mostly RCTs) did not provide any details on harmful consequences of the interventions.<b("F" Discussion#20 Interpretation of the results, taking into account study hypotheses, sources of potential bias or imprecision, and the dangers associated with multiplicity of analyses and outcomes. x74  9G#Annals recommendationsXStructure the discussion section by presenting 1) a brief synopsis of the key findings; 2) consideration of possible mechanisms and explanations; 3) comparison with relevant findings from other published studies & ; 4) limitations of the present study (and methods used to minimize and compensate for those limitations); 5) a brief section that summarizes the clinical and research implications of the work, as appropriate. 0}0 / -  H$>#21 Generalizability (external validity) of the trial findings ?$<$Shadish, Cook and Campbell:  Most experiments are highly local but have general aspirations . That is, there can be a conflict between the localized nature of the information in a paper and the desire of the authors to claim that their findings generalize to other people, in other settings, with comparable interventions, and other outcomes. & Cronbach: a question of external validity. That is, do  instances on which data are collected & generalize to the units, treatments, variables and settings not directly observed ?Z_>$TI%L#22 General interpretation of the results in the context of current evidence M J The result of an RCT is important regardless of which treatment appears better, magnitude of effect, or precision. Readers will want to know how the present trial s results relate to those of other published RCTs. This discussion should be as systematic as possible and not limited to studies that support the results of the current trial.W)Summary2Most journal articles could be improved. CONSORT appropriately  raises the bar on how trials should be reported. Transparency in methods should result in an improved ability of the reader to judge the believability of a paper s findings. See: www.people.vcu.edu/~albest/Guidance/ *, #/d      ! " %&+679BCJK L!M"N#O$P%S&T'X(Y)   0d$(  dr d S  1d   d r d S 1d  d H d 0޽h ? &L333333x&-LYMMM  P$(  r  S ,?d   d r  S @d  d H  0޽h ? &L333333x&-LYMMM  p$(  r  S Nd   d r  S Nd  d H  0޽h ? &L333333x&-LYMMM ( @X$(  Xr X S  td   d r X S td  d H X 0޽h ? &L333333x&-LYMMM$ ) ``$(  `r ` S ,    r ` S    H ` 0޽h ? &L333333x&-LYMMM80___PPT10.G/  ) 0 l(  lX l C     l S K @    H l 0޽h ? ̙3380___PPT10.@or00UWpY)eY  !"#$%&'()*+,՜.+,0     w On-screen ShowMCV/VCU O "Times New Roman Wingdings Ricepaper7The CONSORT* Statement for Reporting Randomized TrialsAcknowledgementsRemember?: Stampfer MJ, et al. Post-menopausal estrogen therapy and cardiovascular disease: ten-year follow-up from the Nurses Health Study. N Engl J Med. 1991;325:756-762.  Later, Contradicted FindingsFrom the JAMA abstractJAMA abstract continuedJAMA abstract continuedAnnals Abstract beginsOther Study DesignsGTitle and Abstract #1 How participants were allocated to interventionsCIntroduction #2 Scientific background and explanation of rationale2Methods #3 Eligibility criteria for participants=#3b The settings and locations where the data were collectedq#4 Precise details of the interventions intended for each group and how and when they were actually administered&#5 Specific objectives and hypotheseso#6 Clearly defined primary and secondary outcome measuresmethods used to enhance the quality of measurements \#7 How sample size was determined and, explanation of interim analyses and stopping rules 5Assessing the likelihood of bias in group assignment#11a Whether or not participants, those administering the interventions, and those assessing the outcomes were blinded to group assignment#12a Statistical methods used to compare groups for primary outcome(s) additional analyses, such as subgroup analyses and adjusted analyses R#13 Flow of participants through each stage (a diagram is strongly recommended). D#15 Baseline demographic and clinical characteristics of each group#16 Number of participants (denominator) in each group included in each analysis and whether the analysis was by intention to treat. State the results in absolute numbers when feasible #17 For each primary and secondary outcome, a summary of results for each group and the estimated effect size and its precision #18 Address multiplicity by reporting any other analyses performed, including subgroup analyses and adjusted analyses, indicating those prespecified and those exploratoryL#19 All important adverse events or side effects in each intervention group DiscussionAnnals recommendations?#21 Generalizability (external validity) of the trial findingsM#22 General interpretation of the results in the context of current evidenceSummary  Fonts UsedDesign Template Slide Titles_Al BestAl Best